The red cell of certain mammals undergoes a metabolic change at birth in which it discards the glycolytic machinery and derives its vital free energy from an as yet poorly understood mechanism. The overall aims of this proposal are to define and characterize this phenomenon in detail. Fetal cells will be separated from the neonatal or adult cells by taking advantage of their differential swelling an glucose media coupled with a conventional density gradient technique. The two cell types will be compared with regards to metabolic ability and membrane permeability. Since limited quantities of such cells are available the recently developed Bessman's technique (66), which is capable of quantitatively measuring the intermediary metabolites from a little as 10 micron 1 packed cells, will be utilized. In this characterization process, the specific stage of fetal development at which the red cell begins to assume adult cell characteristics, as judged by the impermeability of the cell membrane to glucose, will be determined. It is part of our working hypothesis that the non-glycolyzing adult red cell uses certain products of organ metabolism as its metabolic substrate. This is to be explored in detail when the differences between fetal and adult cells have been more fully characterized. It is hoped that the results obtained from this study will shed more light on the attempts to understand the biological relevance for the change in red cell phenotype resulting in a glucose independent adult cell.